title: Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations.
abstract: Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250 mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5 m(2). The median progression-free survival (PFS) of the patients with higher BSA (≥1.5 m(2)) was significantly worse than that of those with lower BSA (< 1.5 m(2)) (10.4 vs. 18.0 months; p = 0.019, log-rank test). Multivariate analysis also showed a significant impact of BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78-2.89; p = 0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p = 0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR-mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR-mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan. Electronic address: ichiha-e@md.okayama-u.ac.jp.
authors.forename: Eiki
authors.initials: E
authors.lastname: Ichihara
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of General Internal Medicine 4, Kawasaki Medical School, Japan.
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hayakawa
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Minami
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Center for Clinical Oncology, Okayama University Hospital, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D049628:Body Size; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Body surface area; Epidermal growth factor receptor mutation; Gefitinib; Non-small cell lung cancer; Progression free survival; Tyrosine kinase inhibitor